A human conserved helix-loop-helix ubiquitous kinase (CHUK) has recently been shown to act in the tumor necrosis factor (TNF)-interleukin-1 (IL-1) signal transduction pathway activating the nuclear factor kappa-B (NF-kappaB) transcriptional activator (C. H Regnier, et al., Cell 90:373-383, 1997). A mouse CHUK has also recently been identified (M. A. Connelly and K. B. Marcu, Cell.Mol.Biol.Res. 41:537-549, 1995). CHUK acts to phosphorylate theinhibitor of NF-kappa-B, I-kappaB, targeting the inhibitor for degradation and allowing NF-kappaB mediated gene activation to occur. NF-kappaB and related proteins control the expression of numerous immune and inflammatory response genes as well as viral genes and have also been implicated in malignant cell transformation (P. A. Baeuerle and D. Baltimore, Cell 87:13-20, 1996; P. A. Baeuerle and T. Henkel, Annu. Rev. Immunol. 12:141-179, 1995). Understanding this signal transduction pathway is therefore of significant biomedical importance.
This indicates that members of the conserved helix-loop-helix ubiquitous kinase family have potential as therapeutic targets and consequently there is a need for identification and characterization of further members of the family.